Top

Pediatric Nephrology

Published in:

01-11-2013 | Original Article

A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study

Authors: Suma Bhat Hoffman, An N. Massaro, Ángel A. Soler-García, Sofia Perazzo, Patricio E. Ray

Published in: Pediatric Nephrology | Issue 11/2013

Abstract

Background

The goal of this study was to assess the value of a urinary biomarker profile comprised of neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates.

Methods

We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n = 10). Urine was collected at baseline, 48 h of illness, and > 24 h post-recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 h and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50 % post-recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data.

Results

Fifteen at-risk newborns had AKI. In the first 48 h of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74 % and specificity of 84 %. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery identified critically ill neonates with AKI.

Conclusions

These findings require validation in larger prospective studies.

Gupta BD, Sharma P, Bagla J, Parakh M, Soni JP (2005) Renal failure in asphyxiated neonates. Indian Pediatr 42:928–934PubMed

Aggarwal A, Kumar P, Chowdhary G, Majumdar S, Narang A (2005) Evaluation of renal functions in asphyxiated newborns. J Trop Pediatr 51:295–299PubMedCrossRef

Karlowicz MG, Adelman RD (1995) Nonoliguric and oliguric acute renal failure in asphyxiated term neonates. Pediatr Nephrol 9:718–722PubMedCrossRef

Selewski DT, Jordan BK, Askenazi DJ, Dechert RE, Sarkar S (2012) Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia. J Pediatr pii: S0022-3476(12)01149

Askenazi DJ, Ambalavanan N, Hamilton K, Cutter G, Laney D, Kaslow R, Georgeson K, Barnhart DC, Dimmitt RA (2011) Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr Crit Care Med 12:e1–e6PubMedCrossRef

Mathur NB, Agarwal HS, Maria A (2006) Acute renal failure in neonatal sepsis. Indian J Pediatr 73:499–502PubMedCrossRef

Agras PI, Tarcan A, Baskin E, Cengiz N, Gurakan B, Saatci U (2004) Acute renal failure in the neonatal period. Ren Fail 26:305–309PubMedCrossRef

Askenazi DJ, Montesanti A, Hunley H, Koralkar R, Pawar P, Shuaib F, Liwo A, Devarajan P, Ambalavanan N (2011) Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr 159(907–912):e901

Kaur S, Jain S, Saha A, Chawla D, Parmar VR, Basu S, Kaur J (2011) Evaluation of glomerular and tubular renal function in neonates with birth asphyxia. Ann Trop Paediatr 31:129–134PubMedCrossRef

10.

Askenazi DJ, Ambalavanan N, Goldstein SL (2009) Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr Nephrol 24:265–274PubMedCrossRef

11.

Drukker A, Guignard JP (2002) Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr 14:175–182PubMedCrossRef

12.

Krawczeski CD, Woo JG, Wang Y, Bennett MR, Ma Q, Devarajan P (2011) Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr 158(1009–1015):e1001

13.

Schmidt-Ott KM (2011) Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury–where do we stand today? Nephrol Dial Transplant 26:762–764PubMedCrossRef

14.

Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543PubMedCrossRef

15.

Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 115:610–621PubMed

16.

Parravicini E, Nemerofsky SL, Michelson KA, Huynh TK, Sise ME, Bateman DA, Lorenz JM, Barasch JM (2010) Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late-onset culture-positive sepsis in very low birth weight infants. Pediatr Res 67:636–640PubMedCrossRef

17.

Paragas N, Qiu A, Zhang Q, Samstein B, Deng SX, Schmidt-Ott KM, Viltard M, Yu W, Forster CS, Gong G, Liu Y, Kulkarni R, Mori K, Kalandadze A, Ratner AJ, Devarajan P, Landry DW, D’Agati V, Lin CS, Barasch J (2011) The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med 17:216–222PubMedCrossRef

18.

Ray P, Acheson D, Chitrakar R, Cnaan A, Gibbs K, Hirschman GH, Christen E, Trachtman H (2002) Basic fibroblast growth factor among children with diarrhea-associated hemolytic uremic syndrome. J Am Soc Nephrol 13:699–707PubMed

19.

Ray PE, Liu XH, Xu L, Rakusan T (1999) Basic fibroblast growth factor in HIV-associated hemolytic uremic syndrome. Pediatr Nephrol 13:586–593PubMedCrossRef

20.

Liu XH, Aigner A, Wellstein A, Ray PE (2001) Up-regulation of a fibroblast growth factor binding protein in children with renal diseases. Kidney Int 59:1717–1728PubMedCrossRef

21.

Soler-Garcia AA, Rakhmanina NY, Mattison PC, Ray PE (2009) A urinary biomarker profile for children with HIV-associated renal diseases. Kidney Int 76:207–214PubMedCrossRef

22.

Tsau YK, Sheu JN, Chen CH, Teng RJ, Chen HC (1996) Decreased urinary epidermal growth factor in children with acute renal failure: epidermal growth factor/creatinine ratio not a reliable parameter for urinary epidermal growth factor excretion. Pediatr Res 39:20–24PubMedCrossRef

23.

Chen L, Liu W (1997) Effect of asphyxia on urinary epidermal growth factor levels in newborns. J Tongi Med Univ 17:144–146CrossRef

24.

Basile DP (2007) The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int 72:151–156PubMedCrossRef

25.

Kiley SC, Chevalier RL (2009) Urinary biomarkers: the future looks promising. Kidney Int 76:133–134PubMedCrossRef

26.

Grandaliano G, Gesualdo L, Bartoli F, Ranieri E, Monno R, Leggio A, Paradies G, Caldarulo E, Infante B, Schena FP (2000) MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy. Kidney Int 58:182–192PubMedCrossRef

27.

Kwon O, Ahn K, Zhang B, Lockwood T, Dhamija R, Anderson D, Saqib N (2010) Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI. Ren Fail 32:699–708PubMedCrossRef

28.

Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, Ambalavanan N (2012) Urine biomarkers predict acute kidney injury in newborns. J Pediatr 161(270–275):e271

29.

Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584PubMedCrossRef

30.

Schwartz GJ, Feld LG, Langford DJ (1984) A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr 104:849–854PubMedCrossRef

31.

Huynh TK, Bateman DA, Parravicini E, Lorenz JM, Nemerofsky SL, Sise ME, Bowman TM, Polesana E, Barasch JM (2009) Reference values of urinary neutrophil gelatinase-associated lipocalin in very low birth weight infants. Pediatr Res 66:528–532PubMedCrossRef

32.

Lavery AP, Meinzen-Derr JK, Anderson E, Ma Q, Bennett MR, Devarajan P, Schibler KR (2008) Urinary NGAL in premature infants. Pediatr Res 64:423–428PubMedCrossRef

33.

Parravicini E (2010) The clinical utility of urinary neutrophil gelatinase-associated lipocalin in the neonatal ICU. Curr Opin Pediatr 22:146–150PubMedCrossRef

34.

Ray PE, Tassi E, Liu XH, Wellstein A (2006) Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome. Am J Physiol Regul Integr Comp Physiol 290:R105–R113PubMedCrossRef

35.

Watanabe K, Ono A, Hirata Y, Fukuda Y, Kojima T, Kobayashi Y (1989) Maturational changes and origin of urinary human epidermal growth factor in the neonatal period. Biol Neonate 56:241–245PubMedCrossRef

36.

Evans NJ, Rutter N, Gregory H (1986) Urinary excretion of epidermal growth factor in the newborn. Early Hum Dev 14:277–282PubMedCrossRef

37.

Di Paolo S, Gesualdo L, Stallone G, Ranieri E, Schena FP (1997) Renal expression and urinary concentration of EGF and IL-6 in acutely dysfunctioning kidney transplanted patients. Nephrol Dial Transplant 12:2687–2693PubMedCrossRef

38.

Mattila AL, Perheentupa J, Pesonen K, Viinikka L (1985) Epidermal growth factor in human urine from birth to puberty. J Clin Endocrinol Metab 61:997–1000PubMedCrossRef

39.

Bagli DJ, Van Savage JG, Khoury AE, Carr M, McLorie GA (1997) Basic fibroblast growth factor in the urine of children with voiding pathology. J Urol 158:1123–1127PubMedCrossRef

40.

Scott SM, Guardian CM, Angelus P, Backstrom C (1991) Developmental pattern of urinary epidermal growth factor in the premature infant and the influence of gender. J Clin Endocrinol Metab 72:588–593PubMedCrossRef

41.

Marler JJ, Fishman SJ, Kilroy SM, Fang J, Upton J, Mulliken JB, Burrows PE, Zurakowski D, Folkman J, Moses MA (2005) Increased expression of urinary matrix metalloproteinases parallels the extent and activity of vascular anomalies. Pediatrics 116:38–45PubMedCrossRef

42.

Kaplan F, Sawyer J, Connors S, Keough K, Shore E, Gannon F, Glaser D, Rocke D, Zasloff M, Folkman J (1998) Urinary basic fibroblast growth factor. A biochemical marker for preosseous fibroproliferative lesions in patients with fibrodysplasia ossificans progressiva. Clin Orthop Relat Res 346:59–65PubMed

43.

Gupta GK, Milner L, Linshaw MA, McCauley RG, Connors S, Folkman J, Bianchi DW (2000) Urinary basic fibroblast growth factor: a noninvasive marker of progressive cystic renal disease in a child. Am J Med Genet 93:132–135PubMedCrossRef

Title: A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study
Authors: Suma Bhat Hoffman
An N. Massaro
Ángel A. Soler-García
Sofia Perazzo
Patricio E. Ray
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 11/2013
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-013-2524-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A novel urinary biomarker profile to identify acute kidney injury (AKI) in critically ill neonates: a pilot study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2013

A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome

Maximizing the sensitivity of the indirect radionuclide cystogram: a retrospective audit

FGF23 and mineral metabolism in the early post-renal transplantation period

A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor as potential biomarkers of acute kidney injury in critically ill children

Long-term outcomes of Shiga toxin hemolytic uremic syndrome

An adolescent boy with acute kidney injury and fever: Answers